Sensitization to oxaliplatin in HCT116 and HT29 cell lines by metformin and ribavirin and differences in response to mitochondrial glutaminase inhibition

Abstract

<b>Aim of study:</b> In the present study, we evaluated the effect of ribavirin and metformin on the sensitivity of oxaliplatin and 5-fluorouracil (5-FU) on colon cancer. <b>Materials and Methods:</b> Cell viability of two commercially available colon cancer cell lines (HT29 and HCT116) were analyzed by sulforhodamine B (SRB) assay. <b>Results:</b> A clinically achievable and nontoxic concentration of ribavirin and metformin showed a significant synergistic effect on oxaliplatin in HT29 and HCT116 cell lines. Ribavirin showed a synergistic effect on oxaliplatin in HT29 (R = 2.93, P < 0.001) and HCT116 (R = 1.71, P < 0.001), while only in HT29 metformin synergized with oxaliplatin by 2.66 (± 0.28, P < 0.01). In addition, both cell lines showed significant differences in response to Compound 968, inhibitor of mitochondrial glutaminase activity. <b>Conclusion:</b> The data suggested that these cell lines not only turn to metabolic different sustainability process after oxaliplatin treatment but that they also have different basal metabolic requirements of glutamine <i>in vitro</i> which can be exploits in the future for colorectal cancer (CRC) treatment and further studies are required.